Evidence map›Paper›PMID 27000758›Full record

ArticleClinical pharmacokinetics2016

Dose- and Formulation-Dependent Non-Linear Pharmacokinetic Model of Paritaprevir, a Protease Inhibitor for the Treatment of Hepatitis C Virus Infection: Combined Analysis from 12 Phase I Studies.

Akshanth R Polepally, Sven Mensing, Amit Khatri, Denise Beck, Wei Liu, Walid M Awni, Rajeev M Menon, Sandeep Dutta

Abstract readClinical Trial, Phase I
PubMed Publisher
In one paragraph

Article in Clinical pharmacokinetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Trial
  2. Trial
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Akshanth R PolepallyAbbVie, Inc., Clinical Pharmacokinetics and Pharmacodynamics, 1 North Waukegan Road, R4PK, AP31-3, North Chicago, IL, 60064, USA. akshanth.r.polepally@abbvie.com.ORCID 0000-0002-5938-6062
Sven MensingAbbVie, Inc., Ludwigshafen, Germany.
Amit KhatriAbbVie, Inc., Clinical Pharmacokinetics and Pharmacodynamics, 1 North Waukegan Road, R4PK, AP31-3, North Chicago, IL, 60064, USA.
Denise BeckAbbVie, Inc., Ludwigshafen, Germany.
Wei LiuAbbVie, Inc., Clinical Pharmacokinetics and Pharmacodynamics, 1 North Waukegan Road, R4PK, AP31-3, North Chicago, IL, 60064, USA.
Walid M AwniAbbVie, Inc., Clinical Pharmacokinetics and Pharmacodynamics, 1 North Waukegan Road, R4PK, AP31-3, North Chicago, IL, 60064, USA.
Rajeev M MenonAbbVie, Inc., Clinical Pharmacokinetics and Pharmacodynamics, 1 North Waukegan Road, R4PK, AP31-3, North Chicago, IL, 60064, USA.
Sandeep DuttaAbbVie, Inc., Clinical Pharmacokinetics and Pharmacodynamics, 1 North Waukegan Road, R4PK, AP31-3, North Chicago, IL, 60064, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectivesParitaprevir is a direct-acting antiviral agent that is a component of approved multidrug regimens used in the treatment of hepatitis C virus (HCV) infection. A population pharmacokinetic model for paritaprevir was developed using data from formulation, bioavailability, and drug-drug interaction studies that evaluated the pharmacokinetics of paritaprevir (coadministered with ritonavir to enhance exposure) with or without ombitasvir and/or dasabuvir at different paritaprevir dose levels.

methodsA non-linear mixed-effects modeling approach was applied to data from 12 phase I, single- and multiple-dose studies that enrolled a total of 369 healthy volunteers. Age, sex, race, ethnicity, body weight, body surface area, body mass index, and baseline creatinine clearance were evaluated as covariates during model development. In addition, the influences of dose, formulation, and concomitant medications (e.g. ombitasvir and dasabuvir) on paritaprevir bioavailability were included in the model.

resultsA two-compartment model with first-order absorption and elimination optimally described paritaprevir plasma concentration-time data. Paritaprevir bioavailability was formulation- and dose-dependent, and increased supraproportionally. The accumulation of paritaprevir was 1.57-fold on repeated dosing compared with the first dose. Coadministration of dasabuvir increased paritaprevir bioavailability by 59 %; however, ombitasvir coadministration did not affect the pharmacokinetic profile of paritaprevir. No subject-specific covariate influenced the paritaprevir pharmacokinetics. The pharmacokinetic model was robust in bootstrap evaluations and was consistent with observed data based on diagnostic goodness-of-fit plots and visual predictive checks.

conclusionThe complex pharmacokinetics of paritaprevir were well described by the model, which can be used as a basis for clinical trial dosing and further evaluations in patients with HCV.

Indexed as

AdolescentAdultAntiviral AgentsBiological AvailabilityCyclopropanesDrug CompoundingDrug InteractionsDrug Therapy, CombinationFemaleHealthy VolunteersHepacivirusHepatitis CHumansLactams, MacrocyclicMacrocyclic CompoundsMaleAntiviral AgentsCyclopropanesLactams, MacrocyclicMacrocyclic CompoundsparitaprevirProlineProtease InhibitorsRibavirinRitonavirSulfonamides

Identifiers

PMID27000758

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.